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Research studies
As of July 2006, the Foundation has approved to fund the following
five research programs.
DT06PA-001-Therapeutic inhibition of angiogenesis
in canine tumors. Read More.
DM06CO-002-Innovative Molecular Targets for Prevention
and Treatment of Canine Hemangiosarcoma. Read
More.
DB06NC-003-Molecular Cytogenetic Characterization
of Canine Hemangiosarcoma as a means of Gene Discovery. Read
More.
DT06CO-004-Sodium valproate to enhance doxorubicin
sensitivity: phase-i evaluation. Read More.
DK06CA-005-Treatment of canine lymphoma with liposome
encapsulated doxorubicin bound to a high affinity ligand. Read
More.
If you would like to donate directly toward one of these grants.
Please click on the "donate to this grant"
button at the end of the description of each grant below
Grant No.
DT06PA-001
Principle Investigator:
Andrei
Thomas-Tikhonenko, Ph.D.
Associate Professor of Pathology
Department
of Pathobiology
University of Pennsylvania
School of Veterinary Medicine
Project Start:
October 1, 2006
Project End:
October 1, 2009*
* With the high potential of clinical trials this grant may be extended
for two more years
Amount of Grant:
$250,000 each year
Title:
Therapeutic inhibition of angiogenesis in canine tumors.
Abstract:
During the last decade, human medicine has witnessed the emergence
of the new generation of cancer drugs, which were rationally designed
to block pathways crucial to tumor growth. One eloquent example
is the inhibitors of angiogenesis (the ingrowth of new blood vessels
into the tumor). All tumors need a blood supply to provide rapidly
dividing cancerous cells with oxygen and nutrients. The task of
generating new vessels is two-fold: it requires an increased production
of pro-angiogenic molecules and a decreased production of anti-angiogenic
molecules. The chief proangiogenic molecule is a protein called
VEGF (for Vascular Endothelium Growth Factor.) The chief anti-angiogenic
molecule is a protein called TSP (for ThromboSPondin.) That most
tumors go to extraordinary lengths to overproduce VEGF and silence
TSP attests to the significance of these molecules.
In our proposal we will focus on three complementary Aims.
1. To generate canine “VEGF trap” proteins capable
of binding and sequestering this pro-angiogenic factor. This will
be achieved by artificially truncating naturally occurring cell
membrane-bound form of VEGF sensors (known as VEGF receptors). The
truncated forms typically do not possess pro-angiogenic activities.
Instead they channel VEGF into dead-end protein-protein interactions.
2. To test anti-angiogenic activities of polypeptides based on
the canine thrombospondin-1 protein. Experimental tumors will be
treated with either polypeptides themselves or DNA fragments encoding
such peptides.
3. To identify molecules capable of re-activate endogenous (tumor-produced)
thrombospondin.
Two classes of molecules are under investigation:
a) compounds that directly increase the half-life of thrombospondin-1
messenger RNA; b) compounds that increase the half-life of the protein
called p53, which is the major activator of thrombospondin.
By the end of the 3d year of NCCF-funded research,
we expect to have begun clinical trials involving at least some
of these newly developed therapeutics. By the very nature of anti-angiogenic
compounds, they can be applied towards a wide range of common canine
neoplasms ranging from Hemangiosarcoma to breast cancers to B-lymphomas,
which collectively account for the majority of cancer-related deaths
in dogs.
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________________________________________________
Grant No.
DM06CO-002
Principle Investigator:
Jaime F. Modiano,
V.M.D., Ph.D.
Associate Professor of Immunology
University of Colorado at Denver & Health Sciences Center
School of Medicine
Project Start:
October 1, 2006
Project End:
October 1, 2009
Amount of Grant:
$250,000 each year
Title:
Innovative Molecular Targets for Prevention and Treatment of Canine
Hemangiosarcoma
Abstract:
Canine hemangiosarcoma (HSA) is an aggressive cancer of blood vessel-lining
(endothelial) cells that occurs commonly in dogs. A major reason
for the death toll is that the cancer develops, progresses and spreads
throughout the body for some time before clinical signs arise and
alert us to its presence.
Current treatments are generally ineffective, thus, there is an
urgent need to understand more about this cancer: knowing why HSA
starts and what controls its progression will allow us to design
and implement better strategies to prevent and treat it.
Specific genetic abnormalities identified as characteristic of specific
cancers, have triggered the development of effective, non-toxic
treatments for these diseases in people. The extent and identity
of such abnormalities in canine cancers, including
HSA, remain unknown. For this project, we will identify genetic
signatures that are associated with all HSAs, as well as those seen
uniquely in specific breeds at high risk for the disease. We will
then examine if these common or breedspecific abnormalities are
amenable as targets for treatment or prevention, respectively. Finally,
we will define the role of stem cells in this disease, to determine
how these cells can be manipulated to improve patient outcomes.
Grant No.
DB06NC-003
Principle Investigator:
Matthew
Breen PhD CBiol MIBiol
Associate Professor of Genomics
Dept.of Molecular Biomedical Sciences
College of Veterinary
Medicine
North Carolina State University
School of Veterinary Medicine
Project Start:
October 1, 2006
Project End:
October 1, 2009
Amount of Grant:
$250,000 each year
Title:
Molecular Cytogenetic Characterization of Canine Hemangiosarcoma
as a means of Gene Discovery.
Abstract:
Canine hemangiosarcoma is an aggressive cancer of the blood vessels
that is relatively common in dogs. A major
reason for the high death toll is that the cancer develops, progresses
and spreads throughout the body for some time
before it reveals clinical symptoms.
Current treatment options are thus generally ineffective and here
is an urgent need to understand more about this cancer. Knowing
why it starts and what controls progression will allow to development
and implement improvement therapies. It has been established that
non-random chromosome aberrations are characteristic of specific
types of many different human cancers and their study has identified
areas of the human genome to be targeted for further research.
In the dog the extent and identity of chromosome aberrations associated
with specific cancers, including hemangiosarcoma, is still largely
unknown. This proposal makes use of major
advances in canine molecular cytogenetics to identify recurrent
chromosome aberrations associated with canine
hemangiosarcoma and then identify genes associated with the cancer.
This project will identify targets for the
development of more appropriate therapies and also to screen dogs
for the presence of hemangiosarcoma at an early stage, so that they
may be begin appropriate treatment before the cancer becomes too
advanced.
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________________________________________________
__________________________
Grant No.
DK06CA-005
Principle Investigator:
Dr
Michael S. Kent
Assistant Professor
Center
for Companion Animal Health (CCAH)
Department of Surgical and Radiological Sciences
School of Veterinary Medicine
University of California, Davis
Project Start:
October 1, 2006
Project End:
October 1, 2007*
* With the high potential of clinical trials this grant may be extended
into a Translational Grant.
Total Amount of Grant:
$50,000
Title:
Treatment of canine lymphoma with liposome encapsulated doxorubicin
bound to a high affinity ligand.
Abstract:
We have recently identified a small chemical molecule that can
bind specifically and extremely strongly to a protein on the cell
surface of lymphoid cancer cells (Non-Hodgkins lymphoma and lymphocytic
leukemia).
The protein receptor is called a4ß1 integrin receptor and
is present in an active form on lymphoid cancer cells. Our chemical
molecule only binds to active form of the protein. We named this
molecule 2A and we believe 2A, when linked to potent cancer drugs,
can effectively deliver the cancer drugs to cancer cells and not
normal cells; therefore we expect the 2A-drug conjugate to be very
effective in killing cancer cells while sparing normal cells. The
goal of this clinical trial is to test this targeted therapy in
dogs with Non-Hodgkins lymphoma.
Further we aim to correlate the binding of the targeted protein
2A to response and overall survival in patients
treated with Doxil-2A.
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